TY - JOUR
T1 - Efficient CRM197-mediated drug targeting to monocytes
AU - Schenk, Geert J.
AU - Haasnoot, P. C. Joost
AU - Centlivre, Mireille
AU - Legrand, Nicolas
AU - Rip, Jaap
AU - de Boer, Albertus G.
AU - Berkhout, Ben
PY - 2012
Y1 - 2012
N2 - Efficient delivery of drugs to specific cellular reservoirs is of particular importance for therapeutics that are not able to pass cellular barriers and that may have unwanted side effects in off-target tissues. Heparin-binding epidermal growth factor (HB-EGF) is expressed on leukocytes and may be targeted for specific drug delivery using cross-reacting material (CRM) 197, a non-toxic variant of diphtheria toxin and exogenous substrate for HB-EGF. We used fluorescently labeled CRM197 and CRM197-coated liposomes to investigate their potential use for drug delivery to leukocytes. We demonstrate that CRM197-guided systems are efficiently taken up by human leukocytes in vitro. CRM197 was also found to specifically target leukocytes in vivo in mice with components of the human immune system (HIS mice) and hamsters. Monocytes represent the most prominent subset of leukocytes that showed highly specific CRM197-mediated uptake. We therefore propose the application of CRM197 as a novel targeting approach in diseases that require the selective treatment of monocytes. Crown Copyright (c) 2011 Published by Elsevier B.V. All rights reserved
AB - Efficient delivery of drugs to specific cellular reservoirs is of particular importance for therapeutics that are not able to pass cellular barriers and that may have unwanted side effects in off-target tissues. Heparin-binding epidermal growth factor (HB-EGF) is expressed on leukocytes and may be targeted for specific drug delivery using cross-reacting material (CRM) 197, a non-toxic variant of diphtheria toxin and exogenous substrate for HB-EGF. We used fluorescently labeled CRM197 and CRM197-coated liposomes to investigate their potential use for drug delivery to leukocytes. We demonstrate that CRM197-guided systems are efficiently taken up by human leukocytes in vitro. CRM197 was also found to specifically target leukocytes in vivo in mice with components of the human immune system (HIS mice) and hamsters. Monocytes represent the most prominent subset of leukocytes that showed highly specific CRM197-mediated uptake. We therefore propose the application of CRM197 as a novel targeting approach in diseases that require the selective treatment of monocytes. Crown Copyright (c) 2011 Published by Elsevier B.V. All rights reserved
U2 - https://doi.org/10.1016/j.jconrel.2011.09.091
DO - https://doi.org/10.1016/j.jconrel.2011.09.091
M3 - Article
C2 - 21982901
SN - 0168-3659
VL - 158
SP - 139
EP - 147
JO - Journal of controlled release
JF - Journal of controlled release
IS - 1
ER -